I learned about migraines by living with someone who had them. A lot. The beast was unpredictable, striking indiscriminately and with a catastrophic force that was unwarranted. I tried to help as best I could; giving space, cutting up apples or banana to help with the nausea, back massages as needed. All the while wishing Stuart would feel better.

The randomness of these attacks did not sit well with the scientist in me. I’m trained to see patterns in biological systems. First you establish a pattern, then you find the cause of the pattern through experimentation. So I approached the cause of the migraines as just that; I needed to find the pattern.

Step 1: What are the causes of the migraines? Every migraineur can list their triggers and Stuart’s were not unique:

• Spicey food
• Chocolate
• Gravox (it is a powder used to make gravy in Australia)
• MSG
• Alcohol
• Cigarette smoke (second hand)

But no matter how I tried, the only pattern I could see is that Gravox was essentially MSG, so it just got recategorised.

I then decided to reverse engineer the problem. Stuart took Imigran to abort his migraines. In fact he swore by it. If I could find out how that worked, then I would have some insight as to what was causing the migraines. This took a bit of sleuthing because pharmaceutical companies tend to tie this type of information up as proprietary.

Luckily I love libraries. I find comfort sitting in the stacks, pulling a dusty set of bound journals off a shelf, reading a paper that leads me to another paper which leads to another paper, which leads…ok, I think you see the pattern here. Researching something takes weeks, months, even years to pull the story together.

It turns out Imigran is the brand name for sumatriptan. Sumatriptan belongs to a class of drugs known as the triptans. Triptans are designed to physically resemble the serotonin molecule and thereby invoke a serotonin response. Serotonin is a neurotransmitter that contributes to feelings of happiness and wellbeing. But this information did not tell me how the drug was acting to stop the migraine. In fact, they still aren’t sure how these serotonin shaped molecules reduce the vasodilation causing the migraine.

There are two ways that this could happen; (1) the molecule itself activates a pathway that causes vasoconstriction, or (2) the molecule could block a pathway causing vasodilation. These are two very different mechanisms, as the first supports a biochemical process and the second stops a biochemical process.

A bit more sleuthing led me to some university based researchers that were proposing that sumatriptan acted to block the nitric oxide pathway. At the time this was new stuff. Sumatriptan became commercially available in the early 1990’s, so it’s now out of patent. When a drug goes out of patent you can publish more readily on it as the research is no longer proprietary. So we needed some time to go by before information came into the public domain.

This group has shown through some very elegant experiments that sumatriptan actually blocks the uptake of nitric oxide (NO) by the blood vessels which causes them to no longer dilate. It’s not that it makes them constrict, it just stops them from dilating any more.

They had two groups of men, migraineurs and non-suffers, and they were able to induce migraines in both by giving the subjects nitroglycerin tablets. These tablets are commonly used during heart attacks as the nitroglycerin causes vasodilation. Great for the heart during a heart attack as it increases blood flow to the heart. Not so good for the brain as the resulting vasodilation results in severe headaches. In fact, you know that the nitroglycerin is working by the presence of the severe headache.

They demonstrated that the nitrite from the nitroglycerin was (1) used by the body as fuel for the nitric oxide pathway to create excess NO and (2) that sumatriptan blocked the uptake of the excess NO. It didn’t remove the excess NO from the body by, let’s say binding with it or breaking it down, so the excess NO is still moving around the body looking for either something to do or waiting to be broken down by other biological processes.

This was what became my lightbulb moment. The light was shining brightly and I was full of confidence. If sumatriptan was working by blocking the uptake of excess NO then all I had to do is see what caused excess NO to be created. Back to the library I went with my list of triggers…

I’m just going to cut to the chase here. Every one of Stuart’s known triggers resulted in the creation of excess NO in the body. I was even able to identify some new triggers which we were able to reverse engineer to be the causes of specific migraines. Things weren’t as random as we thought. I was making progress.

Unfortunately it turns out that just about everything causes the production of NO. I would bet the farm that if you showed those men in those aforementioned studies pictures of puppies and kittens, that it would have resulted in the production of excess NO.

That’s what makes this so complex.

It’s always hard to find balance in a complex system. The ecologist in me was not going to be deterred, because that’s what I do. I find causality in complex systems. So please don’t be discouraged, stick with me. Over the next few weeks I’m going to take you on a journey of my understanding of this complex system and how you can get (some) control of it.

In the meantime, here are some simple lifestyle changes you can make that will help you stop producing excess NO:

• Speak to your physician. Ensure that you are also not taking any medications that activate the nitric oxide pathway. The common medication sildenafil, a.k.a. Viagra, does just this. Under no circumstances should you stop or start taking medications without consulting your healthcare team. Work with them to find out what is going to be best for you. This includes supplements too. There is a huge industry of NO boosting supplements, used primarily by the bodybuilding community, and if you are using any of these you need to talk to your doctor about it.
• Remove preservatives from your diet. If you are eating a balanced diet then you have more than enough naturally occurring fuel for the nitric oxide pathway. But the system can work with artificial sources, recall that the nitrite in the nitroglycerin causes severe headaches in the normal population. You can limit the artificial sources, nitrates and nitrites, by removing preservatives from your diet.
• Get moving. I know this is hard when you have a migraine, but as soon as you can, get walking. Or any kind of movement. You might find relief in the slow rhythmic movement of swimming, a walk in the woods or even ping pong. Simple movements will help burn off the excess NO. But perhaps the best way to use up that NO is “natural remedy”. Viagra creates excess NO that is used up during sexual stimulation. I’ll let you connect the dots here.

As always, remember to consult with your healthcare team before undertaking any lifestyle changes.

Next week we’ll look at how the nitric oxide pathway works. If you understand the beast you can begin to better manage it.

Informed by science, cooked by you.